This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cadherins are cell adhesion proteins involved in adherens junctions and desmosomes and make up the transmembrane component of the cell-cell junctions. Transformation from an epithelial phenotype to an invasive cancerous phenotype has been linked with loss of E-cadherin expression in a number of tissues and cell lines. In addition it has been linked with new expression of N-cadherin, a cadherin not normally expressed in epithelial cells. In fact in some breast cancer cell lines an increase in cell motility and invasive phenotype is directly related to expression of N-cadherin rather than loss of E-cadherin. In light of the role for N-cadherin in mediating cell motility and invasiveness we are studying the regulation of N-cadherin expression at the transcriptional level. Only the chicken N-cadherin gene has been studied to date and that work was only a preliminary evaluation. We are currently mapping DNAse I hypersensitive sites in the promoter and first intron of the Human N-cadherin gene to identify binding sites for transcription factor that regulate this gene. We are also testing luciferase reporter constructs to evaluate the functional role of these hypersensitive sequences in vitro.